VERY-LOW DENSITY LIPOPROTEIN METABOLISM IN DIABETES

糖尿病中的极低密度脂蛋白代谢

• 批准号: 3471106
• 负责人: DAVID W GARBER
• 金额: $ 7.65万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 1987
• 资助国家: 美国
• 起止时间: 1987-05-01 至 1992-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3471106
• 关键词: apolipoproteins; atherosclerosis; blood lipoprotein metabolism; densitometry; disease /disorder model; high performance liquid chromatography; hormone regulation /control mechanism; insulin; lipoprotein lipase; liver metabolism; radiotracer; streptozotocin; thyroid hormones; very low density lipoprotein

Diabetes mellitus is associated with an increased risk of atherosclerosis that may be associated with alterations in lipid metabolism. The overall objective of this study is to determine the effects of experimentally-induced diabetes mellitus on very-low-density-lipoprotein (VLDL) metabolism in the rat. In order to accomplish this objective, the following specific aims will be pursued: 1) Clearance of 125I-VLDL apolipoproteins by diabetic and control rats will be measured in vivo and in isolated liver perfusions. In particular, the presence or absence of selective clearance of either of the predominant forms of apolipoprotein B will be determined. 2) The involvement of insulin and thyroid hormones in the control of apolipoprotein clearance in diabetics will be investigated. 3) The degree of glycosylation of apolipoproteins from diabetic animals will be measured, and the effects of glycosylation on apolipoprotein clearance will be determined. 4) Activity of lipoprotein lipase and hepatic lipase will be measured in diabetic rats. The effects of glycosylation of apolipoproteins on lipoprotein lipase and hepatic lipase activities will be investigated. The model of diabetes to be used in these experiments will be the streptozotocin-diabetic rat. Diabetes will be induced by injection of streptozotocin at a dose of 65 mg/kg body weight. Rats will be maintained on insulin for one week in order to minimize direct toxic effects of streptozotocin, then insulin will be withdrawn for at least 3 days prior to any experimental procedures.

糖尿病与动脉粥样硬化的风险增加有关 这可能与脂质代谢的改变有关。整体而言 本研究的目的是确定 实验性糖尿病对极低密度脂蛋白的影响 (极低密度脂蛋白)在大鼠体内的代谢。为了实现这一目标， 将实现以下具体目标：1)清除125I-极低密度脂蛋白 糖尿病大鼠和对照组大鼠的载脂蛋白将在体内和 在孤立的肝脏灌流中。特别是，存在或不存在 选择性清除载脂蛋白B的任何一种主要形式 将会被确定。2)胰岛素和甲状腺激素的参与 糖尿病患者载脂蛋白清除的控制将被研究。 3)糖尿病动物载脂蛋白的糖基化程度 将被测量，糖基化对载脂蛋白的影响 通行证将会确定。4)脂蛋白脂酶活性和 将对糖尿病大鼠的肝脏脂肪酶进行检测。的影响 载脂蛋白在脂蛋白脂肪酶和肝脂酶上的糖基化 将对活动进行调查。糖尿病模型将在这些方面使用 实验将链脲佐菌素诱导成糖尿病大鼠。糖尿病将会是 以65 mg/kg体重注射链脲佐菌素诱导。 大鼠将维持一周的胰岛素，以减少直接 链脲佐菌素的毒性作用，那么胰岛素将被停用 在任何实验程序前至少3天。